Stereoselective Heterocycle Synthesis via Zn(II) Promoted Metalloamination/Cyclization

项目总结 碳-氮结构的新的、高度立体控制反应的阐明 碳-碳键仍然是化学合成的中心目标。多年来，各种 这一领域的发现使各种重要药物的有效制备成为可能。 造福了人类。这项拨款申请要求支持首席调查员的 有机锌(II)促进杂环合成领域的新项目。本申请 重点介绍了一种新的具有潜在功能的分子内C-C-的发现和合成应用 N/C-锌键形成级联，涉及添加官能化的锌酰胺，来源于N，N-N- 二甲基肼，到烯、二烯、烯炔、乙烯基环丙烷和乙烯基环丁烷。我们相信 这种方法将作为立体控制合成的载体得到相当大的应用。 与生物相关的小分子。 在建议的资助期内发现的新化学的应用应该是 易适用于合成多种立体化学富含杂环的药物 意义。在这项拨款申请中描述的研究计划预计将提供有价值的 洞察新的反应类型，应有助于阐明对 分子内连续C-N/C-Zn(从而：C-N/C-电子)键形成的发展 立体控制小分子合成的背景。

PROJECT SUMMARY The elucidation of new, highly stereocontrolled reactions for the construction of carbon–nitrogen and carbon-carbon bonds remains a central goal of chemical synthesis. Over the years, various discoveries in this area have enabled the efficient preparation of a wide variety of important medicinals that have benefited humanity. This grant application requests support for the Principal Investigator's new projects in the area of organozinc(II)-promoted heterocycle synthesis. The present application emphasizes the discovery and synthetic application of a new and potentially powerful intramolecular C- N/C-Zn bond forming cascade involving the addition of functionalized zinc amides, derived from N,N- dimethylhydrazines, to allenes, dienes, enynes, vinylcyclopropanes and vinylcyclobutanes. We believe this method will receive considerable utilization as a vehicle for the stereocontrolled synthesis of biologically relevant small molecules. The application of the new chemistry discovered during the proposed grant period should be readily applicable to the synthesis of numerous stereochemically rich heterocycles of pharmacological significance. The research program described in this grant application is expected to provide valuable insight into new reaction types that should serve to elucidate specific factors that are critical to the development of consecutive intramolecular C-N/C-Zn (and thus: C-N/C-Electrophile) bond formation in the context of stereocontrolled small molecule synthesis.